Pediatric Department of Qilu Hospital, Shandong University, #107 Wenhuaxi Road, Jinan, China.
Brain Res. 2013 Jun 26;1519:78-86. doi: 10.1016/j.brainres.2013.04.047. Epub 2013 May 4.
Maternal infection during pregnancy is associated with an increased risk of neurodevelopmental injury. Our aim was to investigate whether prenatal immune challenge could alter susceptibility to seizure-induced brain injury in adulthood. Pregnant Wistar rats were injected intraperitoneally with lipopolysaccharide (LPS) or normal saline (NS) at days 15 and 16 of gestation. At postnatal day 45, seizure susceptibility was assessed in response to lithium-pilocarpine (LiPC) in adult offspring. Four groups were studied, including normal control (NS-NS), prenatal inflammation (LPS-NS), adult seizure (NS-LiPC), and "two-hit" (LPS-LiPC) groups. Our results demonstrated that adult rat offspring of LPS-exposed dams showed significantly greater susceptibility to LiPC-induced seizures, as well as enhanced hippocampal neuronal injury after seizures. Furthermore, animals in the "two-hit" group performed significantly worse than those from the NS-LiPC group in the open field test and Morris water maze. Our findings suggest that prenatal immune activation can cause a long-lasting increase in seizure susceptibility and predispose the brain to the damaging effect of seizures later in life.
母体妊娠期间感染与神经发育损伤的风险增加有关。我们的目的是研究产前免疫挑战是否会改变成年后对癫痫引起的脑损伤的易感性。在妊娠第 15 和 16 天，将脂多糖（LPS）或生理盐水（NS）腹腔内注射给怀孕的 Wistar 大鼠。在出生后第 45 天，用锂-匹罗卡品（LiPC）评估成年后代的癫痫易感性。研究了包括正常对照组（NS-NS）、产前炎症组（LPS-NS）、成年癫痫组（NS-LiPC）和“双打击”组（LPS-LiPC）在内的四个组。我们的结果表明，暴露于 LPS 的母鼠的成年大鼠后代对 LiPC 诱导的癫痫发作具有明显更高的易感性，并且在癫痫发作后海马神经元损伤也增强。此外，“双打击”组动物在旷场试验和 Morris 水迷宫中的表现明显比 NS-LiPC 组差。我们的研究结果表明，产前免疫激活可导致癫痫易感性的持久增加，并使大脑易受生命后期癫痫发作的损害。
